Protective role of gamma interferon in experimental pulmonary paracoccidioidomycosis.
We have developed a murine model of pulmonary infection by Paracoccidioides brasiliensis in which resistance was associated with immunological activities governed by gamma interferon (IFN-gamma). To better characterize this model, we measured type 1 and type 2 cytokines in the lungs and investigated the effect of endogenous IFN-gamma depletion by monoclonal antibodies in the course of infection of susceptible (B10.A) and resistant (A/Sn) mice. At weeks 4 and 8 after infection, lungs from susceptible animals presented levels of IFN-gamma, interleukin-4 (IL-4), IL-5, and IL-10 higher than those in resistant mice. In both mouse strains, neutralization of endogenous IFN-gamma induced exacerbation of the pulmonary infection, earlier fungal dissemination to the liver and spleen, impairment of the specific cellular immune response resulting in significantly lower delayed-type hypersensitivity reactions, and increased levels of immunoglobulin G1 (IgG1)- and IgG2b-specific antibodies. Histopathological analysis demonstrated that depletion of IFN-gamma changes the focal granulomatous lesions found in the lungs of B10.A and A/Sn mice into coalescent granulomata which destroy the pulmonary architecture. These results suggest that irrespective of the mouse strain, IFN-gamma plays a protective role and that this cytokine is one major mediator of resistance against P. brasiliensis infection in mice.
Cano
L E
LE
Departamento de Imunologia, Instituto de Ciências Biomédicas da Universidade de São Paulo, Brazil.
Kashino
S S
SS
Arruda
C
C
André
D
D
Xidieh
C F
CF
Singer-Vermes
L M
LM
Vaz
C A
CA
Burger
E
E
Calich
V L
VL
D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000502:physiology*; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000473:pathology
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D007371:Interferon-gamma